Recently, cyclopeptides having antifungal activities have been discovered in the fermentation liquid of certain fungi. Most of such cyclopeptides are cyclohexapeptides, generally called echinocandins, such as WF11899, and echinocandin. These cyclopeptides can be chemically modified to obtain semisynthetic antibiotics which can be used clinically.
The compound of formula I having the cyclohexapeptide structure is a natural product obtained by fermentation. The compound can be used as the raw material for synthesizing the compound of formula II. The preparation method of formula I can be found in the preparation methods disclosed in U.S. Pat. Nos. 5,202,309, 5,194,377 and 6,610,822.
The acetate of the compound according to formula II can be used as the peptide antibiotics for treating invasive aspergillosis, candidosis in esophagus, intra-abdominal abscess, pleurisy, abdominal infection caused by Candida spp, and the fever caused by unidentified pathogens in neutropenia patient. At present, the acetate of the compound according to formula II (caspofungin acetate, with the trade name “CANCIDAS”) is sold in many countries as antifungal agent administrated intravenously.

The compound of formula I is hard to crystallize, and generally, it is amorphous. For the end use of the compound according to formula I as a therapeutic or for the use thereof as the intermediates for the compound according to formula II, it is desirable to obtain crystals with high purity. U.S. Pat. No. 5,336,756 has disclosed a crystallization method using aqueous propanol as crystallizing solvent. Crystal A obtained by the method has peaks at the following 2θ angles in the X-ray diffraction pattern: 2.16±0.2°, 4.26±0.2°, 8.06±0.2°, 9.06±0.2°, 13.34±0.2°, 15.06±0.2°, 17.70±0.2°, 20.96±0.2°, 26.28±0.2°. It is concluded in U.S. Pat. No. 5,336,756 that except for n-propanol, other solvent is unsuitable for crystallization, but the method is time-consuming (12-20 hrs), low-yield (85.2% at the most), and unsuitable for industrial production.
Therefore, it is urgent to provide a method for preparing the crystal of the compound according to formula I and the crystal obtained, and said method should be readily and quickly conducted, and high-yielding.